By correlating the antigenic expression on fetal lymphoid cells with the phenotypic determinant on malignant lymphocytes, we will establish the stage during differentiation at which leukocytes are susceptible to carcinogenic agents. Malignant transformation has been considered an arrest in cell differentiation. Thus, a characterization of neoplastic leukocytes will provide information to determine at what particular stage of normal leukocyte differentiation the neoplastic event occurred. We first studied the development of B cells in the fetal liver. We found that heterologous and monoclonal reagents can identify B-cell subsets as early as 12 to 13 weeks gestation. In a similar approach, we began to study different macrophage populations in the fetal liver and bone marrow. Our results, using the double staining methods developed in this laboratory, show populations of macrophages displaying various phenotypes throughout gestation. We plan to examine pre-B cells, and different macrophage populations, particularly in the liver, thymus, and bone marrow, for the expression of tumor-associated antigens, since we have observed these populations to change with fetal development. This study will contribute to the basic understanding of the origin of malignancy by identifying the susceptible stage during leukocyte differentiation at which a carcinogenic event has occurred and determine prognosis and treatment, since the course of disease and selection of therapy can be determined by the extent of cell maturation. (MI)